Evidence has accumulated which links changes in putative neurotransmitter functions, the cerebral macromolecules, lipid metabolism and membrane structure to morphine analgesia and tolerance. We propose to study (1) the role of gene expression on the regulation of macromolecule biosynthesis in tolerant animals and its relation to morphine tolerance development. We are seeking to broaden the understanding of the effect of chronic morphine on gene expression. (2) the effects of narcotics on the structure and function of synaptic membrane. We plan to determine the chemical nature of some membrane constituents which have proven to be essential in narcotic-membrane binding, and to determine the role of these membrane constituents in modifying synaptic function which leads to changes of narcotic actions. It is our hope to elucidate those changes in membrane structure which are related to alterations in synaptic function caused by chronic morphine treatment. BIBLIOGRAPHIC REFERENCES: Tseng, L.F., Loh, H.H. and Wei, E.T.: Effects of clonidine on morphine withdrawal signs in the rat. Europ. J. Pharmacol. 30: 93-99, 1975. Tseng, L.F., Menon, M.K. and Loh, H.H.: Brain lesions modifying the abstinence signs in morphine-dependent rats. Neuropharmacology 14:247-250, 1975.